The present invention pertains to an apparatus and method for manipulating, transporting, and analyzing a large number of microscopic samples of a liquid or of materials including cells currently or formerly in liquid suspension.
Chemistry on the micro-scale, involving the reaction and subsequent analysis of quantities of reagents or analytes of order microliters or smaller, is an increasingly important aspect of the development of new substances in the pharmaceutical and other industries. Such reaction and analysis may accommodate vast libraries containing as many as a million compounds to be reacted and analyzed under various conditions. Significant problems associated with current technologies as applied to chemical analysis of vast numbers (potentially on the order of hundreds of thousands or millions per day) of compounds include the problem of handling vast numbers of compounds and reactions in parallel.
Existing technology relies on 96-, 384-, or 1536-well plates containing quantities between approximately 1 microliter and 1 milliliter of liquid compound per well, and, generally, involves chemical reactions and analysis in wells disposed with single openings on flat, two-dimensional surfaces such as silicon chips. It is not practical to apply existing technology in the art to form million-well disks. There is a need, therefore, for new approaches that permit the analysis of a million samples in a laboratory format.
In accordance with one aspect of the invention, in one of its embodiments, there is provided a method for selecting samples having specified properties from a library of samples. The method has the steps of:
a. providing a platen having two substantially parallel planar surfaces and a plurality of addressable through-holes disposed substantially perpendicularly to the planar surfaces;
b. loading a first sample in liquid form into at least one of the through-holes;
c. adding a second sample into the at least one of the through-holes for permitting a reaction between the first sample and the second sample; and
d. characterizing the reaction in the through-hole in terms of the specified properties.
In accordance with alternate embodiments of the invention, each through-hole may be dimensioned so as to maintain a liquid sample therein by means of surface tension, and may have a volume less than 100 nanoliters. The plurality of addressable through-holes may have a density in excess of 108 per square meter.
In accordance with further alternate embodiments of the invention, the step of loading a first sample may include drawing the sample from a planar surface by capillary action. The platen may be brought into contact with a reservoir of liquid and rotated about an axis perpendicular to the surface of the reservoir or about at least one of an axis perpendicular to the surface of the reservoir and an axis parallel to the surface of the reservoir. The method may include the further step of maintaining a humid atmosphere for preventing evaporation of the first sample or coating the liquid sample with a monolayer for preventing evaporation of the first sample.
In accordance with a further aspect of the present invention, a method is provided for preparing a plurality of combinations of members of a first set of samples in liquid form with members of a second set of samples in liquid form, the method comprising:
a. providing a first perforated platen having through-holes and a second perforated platen having through-holes;
b. loading a first set of samples in liquid form into the through-holes of the first perforated platen;
c. loading a second set of samples in liquid form into the through-holes of the second perforated platen;
d. registering the through-holes of the first perforated platen with the through-holes of the second perforated platen; and
e. combining the first set of samples with the second set of samples.
In accordance with yet further aspects of the present invention, there are provided methods for mixing and diluting liquid samples. The methods have steps of loading one set of liquid samples into through-holes of a first platen and loading another set of liquid samples into through-holes of a second platen, and then disposing a surface of the first platen in contact with a surface of the second platen in such a way as to register at least one through-hole of the first platten with at least one of through-hole of the second platten for permitting mixing of the liquid samples of the respective sets.
In accordance with another aspect of the present invention, there is provided a system for analyzing a plurality of liquid samples. The system has a platen having two substantially parallel planar surfaces and a plurality of through-holes having apertures and walls, a source of optical radiation for illuminating at least one through-hole along an optical axis, and an optical arrangement for analyzing light emanating from the at least one through-hole.